The successful colonization of the host is a process required for most microorganisms to cause infections in animals and humans. Microbial adhesion is the first crucial step in a series of events that can eventually lead to disease. Pathogenic microorganisms colonize the host by attaching to host tissues or serum conditioned implanted biomaterials, such as catheters, artificial joints, and vascular grafts, through specific adhesins present on the surface of the bacteria. MSCRAMM™s (Microbial Surface Components Recognizing Adhesive Matrix Molecules) are a family of cell surface adhesins that recognize and specifically bind to distinct components in the host's extracellular matrix. Once the bacteria have successfully adhered and colonized host tissues, their physiology is dramatically altered and damaging components such as toxins and proteolytic enzymes are secreted. Moreover, adherent bacteria often produce a biofilm and quickly become more resistant to the killing effect of most antibiotics.
S. aureus causes a spectrum of infections that range from cutaneous lesions such as wound infections, impetigo, and furuncles to life-threatening conditions that include pneumonia, septic arthritis, sepsis, endocarditis, and biomaterial related infections. S. aureus is known to express a repertoire of different MSCRAMMs that can act individually or in concert to facilitate microbial adhesion to specific host tissue components. MSCRAMMs provide an excellent target for immunological attack by antibodies, in particular monoclonal antibodies. The presence of the appropriate anti-MSCRAMM high affinity antibodies can have a double-edged attack, first the antibodies can prevent microbial adherence and second the increased levels of MSCRAMM antibodies facilitate a rapid clearance of the organism from the body through opsonophagocytic killing.
However, it has still remained a problem to identify and utilize the information concerning MSCRAMM™S from S. aureus such as the ClfA protein to generate effective monoclonal antibodies because of the variability in the binding properties of the different MSCRAMM™s and their role in infectivity and spread of bacterial infections. In particular, it has been a problem to develop monoclonal antibodies which can bind to ClfA and which can be use to inhibit or impair the binding of staphylococcal ClfA to fibrinogen or fibrin and thus be useful in methods of preventing or treating staphylococcal infections. It has thus remained a highly desirable goal in the field of infectious diseases to develop monoclonal antibodies and other compositions which are successful in treating and preventing a wide variety of staph infections, particularly by inhibiting or impairing the bacteria's ability to bind to fibrinogen or fibrin.